ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
Bone morphogenetic protein 2 inhibits hepatocellular carcinoma growth and migration through downregulation of the PI3K/AKT pathway.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- SEMA4F Regulates the Malignant Phenotype of Hepatocellular Carcinoma Cells Through the PI3K-Akt Pathway.Journal of hepatocellular carcinoma · 2026Article
- Expression of miR-15b-5p and toll-like receptor4 as potential novel diagnostic biomarkers for hepatitis C virus-induced hepatocellular carcinoma.Non-coding RNA research · 2025Article
- Bone Morphogenetic Protein 13 Has Protumorigenic Effects on Hepatocellular Carcinoma Cells In Vitro.International journal of molecular sciences · 2023Article
- Bone morphogenic protein-7 (BMP-7) polymorphism: Susceptibility to cirrhosis and hepatocellular carcinoma after viral hepatitis in Egyptian patients.Clinical and experimental hepatology · 2023Article
- Inhibition of the BMP pathway prevents development of Barrett's-associated adenocarcinoma in a surgical rat model.Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus · 2022Article
- Romidepsin hepatocellular carcinoma suppression in mice is associated with deregulated gene expression of bone morphogenetic protein and Notch signaling pathway components.Molecular biology reports · 2021Article
- Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis.Nature metabolism · 2020Article
- Bone morphogenetic protein-9 promotes the proliferation of non-small cell lung cancer cells by activating PI3K/Akt and Smad1/5 pathways.RSC advances · 2020Article
- High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells.Frontiers in oncology · 2020Article
- ACVR1 Function in Health and Disease.Cells · 2019Review
- Oncogenic value of microRNA-15b-5p in hepatocellular carcinoma and a bioinformatics investigation.Oncology letters · 2019Article
- Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling.Cell death & disease · 2018Article
- Identification of key pathways and genes inOncoTargets and therapy · 2018Article
- BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway.Aging · 2017Article
- Article
- Review
- HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma.Oncotarget · 2016Article
- Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells.Frontiers in pharmacology · 2016Review
- Calreticulin down-regulation inhibits the cell growth, invasion and cell cycle progression of human hepatocellular carcinoma cells.Diagnostic pathology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Previous studies have suggested that abnormal expression of BMP-4, BMP-7, and BMP-9 is correlated with tumor progression in HCC, but the role played by BMP-2 in HCC has not yet been reported. To determine the role of BMP-2 in HCC, we first investigated the effect of exogenous BMP-2 on the growth of the cell lines HCC SK-Hep-1, Hep G2, and Hep 3B. Next, we studied the function of BMP-2 in SK-Hep-1 HCC cell line using a recombinant lentivirus vector to deliver BMP-2. We also used siRNA to silence endogenous BMP-2 expression in the HCC Hep 3B cell line. Then, cell growth and migration were assayed in vitro using WST-8, wound-healing, and transwell invasion assays. Cellular apoptosis and cell-cycle distribution were assessed using flow cytometry. We also investigated the effects of BMP-2 overexpression and knockdown on the expression of proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2), phosphorylated AKT (p-AKT), phosphoinositide 3-kinase p85α (PI3Kp85α), Bax, Bcl-2, caspase-3, cleaved caspase-3, p21, and cyclin E. As a result, we observed that BMP-2 inhibited the proliferation of HCC cells. Furthermore, HCC cell proliferation and migration were significantly diminished by BMP-2 overexpression, as was indicated by WST-8, would healing, and transwell assays, while knockdown of BMP-2 led to an increase in proliferation and migration of Hep 3B cells. BMP-2 overexpression significantly increased the susceptibility of SK-Hep-1 cells to low-serum-induced apoptosis, while BMP-2 knockdown reduced the susceptibility of Hep 3B cells. Overexpression of BMP-2 induced G1 phase arrest through upregulation of p21. When BMP-2 expression was elevated in SK-Hep-1 cells, the expression of PI3Kp85α, p-AKT, PCNA, and MMP-2 declined. These results suggest that BMP-2 exerts an inhibitory effect on the growth and migration of HCC cells, possibly via a blockade of PI3K/AKT signaling.
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